系统性红斑狼疮(SLE)的发病有显著性别差异，明确这种性别二态性的形成机制对探明病因及个性化治疗十分重要。我们前期利用转录组测序及生物信息学分析发现IFN调节基因44样蛋白(IFI44L)是SLE的易感基因并可能参与其性别二态性的形成。进一步分析发现该基因高表达于脾脏及淋巴细胞，其表达受到雌激素的诱导，可能参与了IFN-α介导的SLE发病过程。据此，我们提出假说：雌激素可能通过IFN1信号通路诱导IFI44L参与SLE性别二态性的形成。为此，我们利用Ifi44l敲除小鼠，系统分析在雌激素干预下不同性别小鼠表型差异，IFN1信号通路关键基因表达差异及对B细胞功能的影响，深入研究其生物学功能。同时将敲除鼠与MRL/lpr小鼠杂交，通过分析Ifi44l-/-Faslpr/lpr狼疮鼠性别间表型差异，明确其在SLE病理发生及其性别二态性中的作用，为筛选SLE不同性别间个体化治疗靶点提供理论依据。

The incidence of systemic lupus erythematosus (SLE) has the significant sexual dimorphism, which is of great importance for the identification of the etiology and the personalized treatment. IFN-induced protein 44-like gene (IFI44L) is a newly discovered member of the type I interferon-stimulated gene family and is closely related to viral infection and immune inflammatory diseases. By using the whole transcriptome sequencing (RNA-Seq) and bioinformatics analysis, it has been found that the IFI44L gene is a susceptibility gene for SLE and probably play a role in the formation of the SLE sexual dimorphism. Further analysis has revealed that the IFI44L gene is highly expressed in the spleen and lymphocytes, and its expression level is significantly regulated by the estrogen, which may be involved in the pathogenesis of SLE mediated by IFN-α. However, the underlying specific mechanism and its effect on the formation of the SLE sexual dimorphism are still unclear. Based on the above results, we hypothesize that the estrogen may induce IFI44L to participate in the SLE sexual dimorphism by activating type I interferon (IFN1) signaling pathway. Here, Ifi44l whole-body knockout mice models will be established and applied. Under the intervention of estrogen, the phenotypic differences of different sex mice, the differentially expressed key genes in IFN1 signaling pathway and the effect on the proliferation and development of B cells will be systematically analyzed to further study the biological function of the gene. Additionally, Ifi44l knockout mice will cross with MRL/lpr mice, and the phenotypic differences between different sexes of Ifi44l-/-Faslpr/lpr lupus mice will be assessed to determine its role in the SLE pathogenesis and the sex dimorphism. Our study will provide a new understanding of the biological mechanisms of SLE and a theoretical basis for screening individualized therapeutic targets between different genders with SLE.